The long-range objective is to decrease the risk from radionuclide-induced cancer by removing radioactive elements from the body with chelating agents that are effective and safe. Specific aims are as follows: (1) The effectiveness of DTPA in decreasing the risk from actinide-induced bone cancer will be quantified. In 1973-1976, seventeen beagles were injected with 239Pu or 241Am and then given protracted therapy with zinc-DTPA or calcium-DTPA. Without the DTPA therapy, bone cancers should now have appeared in about 14 of these 17 beagles. As of May 1983, five of the 17 dogs had died with osteosarcomas, two from causes apparently unrelated to irradiation, and the remaining ten were alive and healthy. The survivors will continue to be observed throughout their lifespans to establish the effect of radionuclide removal on decreasing the cancer frequency and delaying the tumor appearance time. (2) Selected new chelating agents that appear superior to DTPA in mice will be evaluated in beagles. Since DTPA removes only part of the radioactivity, only part of the cancer risk is eliminated. Therefore, better chelating agents are needed. Drs. Kenneth Raymond, Patricia Durbin, and colleagues at Berkeley, have synthesized about 30 new chelating agents and tested them in mice. Two of the more promising agents [LICAM(S) and LICAM(C)] have already been tested in beagles at the University of Utah. Other highly promising agents, at present, include Desferri; CAM(C) and 3-HOPOCAM. The plan is to test about two new chelating agents per year in beagles for effectiveness in Pu removal and the lack of acute toxicity. The most promising agent or agents passing this test will then be further rested by repeated administration to beagles. The aim is to find new chelating agents thast are superior to DTPA and might be appropriate for the treatment of persons internally contaminated with radioactivity.